Gap junction heterogeneity in reentrant ventricular tachycardia.

The cells of all tissues are coupled by gap junctions, with the exception of blood and adult skeletal muscle cells. Gap junctions provide for homoeostasis and integrative function by mediating the exchange of ions and chemical second messenger molecules between adjacent cells. The electrical signaling provided by these specialized intercellular junctions is perhaps best understood in the heart, where their abundance serves to provide low electrical resistance pathways for current flow — ensuring fast and efficient transfer of the propagating cardiac action potential throughout the working myocardium. This role of the gap junction, or nexus as it was then called, was best demonstrated by Barr et al. [1] when they correlated the block of cardiac action potential propagation with disruption of the gap junction structure by extracellular hypertonic sucrose solutions [1]. Studies since the 1960s investigated the membrane structure of gap junctions, and the only structural changes noted were associated with irreversible uncoupling procedures [2–4]. These irreversible structural changes occurred after prolonged acidification or mechanical trauma and were first described as the “healing-over” phenomenon of the heart [5,6]. Gap junctions were otherwise still regarded as relatively static structures that changed their conformation only after severe pathological events such as a healing infarct or surgical repair. Todaywe know this not to be the case. The channel function and molecular composition of cardiac gap junctions was elucidated in the mid-1980s, and the half-life of connexin43 (Cx43), the primary gap junction protein of the ventricular